Peavy struck out 10 in 8 1/3 innings and Blanco homered twice, leading San Diego to a 6-3 win over the San Francisco Giants.
Blanco helped power the San Diego offense with two solo drives but it was the way the catcher worked with Peavy that had the Padres talking.
"Henry is as good as anybody I've been with about getting in the game and doing what we talked about," Peavy said. "I spend a lot of time talking to Henry a lot about what I wanted to do to be successful."
Whatever the pair talked about worked against the Giants. Although Peavy said he did not have his best stuff, he held the Giants in check, taking a five-hitter into the ninth inning.
"He was outstanding," Blanco said. "His breaking stuff was working pretty good, he was aggressive. He kept pounding the strike zone all night."
Peavy (1-1) allowed three runs and seven hits. The 2007 NL Cy Young Award winner was sharper than in the season opener on Monday when he got the decision in a 4-1 loss to the Los Angeles Dodgers, crediting a change he made in throwing his slider.
"I started throwing a little more of a slurve," he said. "I was taking a little bit off it because I don't want to throw everything at the same speed."
Manager Bud Black has anointed Blanco as Peavy's personal catcher, noting the great communication between the pair.
"Both guys are in synch, and it is something we started seeing at the end of spring training," Black said. "Henry is getting to know Jake. He does all the things that a pitcher looks for."
Adrian Gonzalez helped break open the game with a bases-loaded double in the fifth and finished with three RBIs.
Blanco tied his career high with two drives off Jonathan Sanchez (0-1), the second one leading off the fifth to break a 1-all tie. Gonzalez added a two-out, three-run double in the inning to knock Sanchez from the game and give the Padres a 5-1 lead.
"I got a couple of pitches to hit," Blanco said.
The win gave the Padres a 4-2 record, matching their high mark for games over .500 from last season when it happened five times early on, the last coming on April 15 when San Diego was 8-6.
Peavy, who gave up four runs -- three earned -- in seven innings against the Dodgers, was more consistent as he worked quickly through the San Francisco lineup. Peavy retired the first nine batters before Randy Winn's leadoff double in the fourth.
He left after Fred Lewis' RBI double with one out in the ninth drove in Winn, who led off with an another double. Winn finished 3-for-4 and scored two runs.
"I wanted to finish it," Peavy said. "I didn't have great stuff so I had to battle."
Heath Bell got the final two outs for his third save.
"We're facing one of the better pitchers in the game, but I thought our guys battled," San Francisco manager Bruce Bochy said. "We got three runs and you don't expect to score a lot off Jake."
Sanchez started strong by striking out five of his first six batters. He then allowed a homer to Blanco leading off the third.
Sanchez allowed five runs and four hits, walked five and struck out seven.
"I was getting ahead until the fifth inning and I just lost my release point," Sanchez said. "I got behind guys, and I walked a guy, and [Gonzalez] got the big hit."
San Francisco scored its first run in the fourth after a mistake by Blanco.
After Winn led off with a double and moved to third on a single by Edgar Renteria, Black called for a pitchout with Lewis batting.
Renteria took off from first as Peavy delivered the pitch to Blanco. The catcher never looked over at Winn, but instead snapped a throw to Gonzalez at first base. When Blanco threw the ball, Winn took off for home and scored easily as Renteria got caught in a rundown before being tagged out.
The Giants scored in the seventh on Bengie Molina's sacrifice fly after Lewis' leadoff triple.
Although Peavy is 12-8 in his career against the Giants, he had lost five of eight starts coming in, including both starts last season. ... Blanco has homered twice in a game three times, the last coming on April 10, 2004, at Detroit. ... Gonzalez received his Gold Glove award from last season. ... This series features the past two NL Cy Young Award winners with Peavy, the 2007 recipient, and last season's winner, Tim Lincecum, scheduled to start for San Francisco on Sunday.